Sissy capitalizes on the size of her thumbs by becoming a hitchhiker and subsequently travels to New York, United States (U.S.). The character becomes a model for The Countess, a male homosexual tycoon of feminine hygiene products. The Tycoon introduces Sissy to a staid Mohawk named Julian Gitche, whom she later marries. In her later travels, she encounters, among many others, a sexually open cowgirl named Bonanza Jellybean and an itinerant escapee from a Japanese internment camp happily mislabeled The Chink. The Chink is presented as a hermeticmystic and, at one point. writes on a cave wall, "I believe in everything; nothing is sacred. I believe in nothing; everything is sacred." and frequently says "Ha Ha Ho Ho and Hee Hee." A flock of whooping cranes also makes frequent appearances throughout the novel, which includes details of their physical characteristics and migratory patterns. Robbins also inserts himself into the novel (as a character).

Cowgirls ... has been considered a hippie novel by Van Sant.[3] Robbins writes short chapters filled with philosophical asides and quips (such as noting that because amoebae reproduce by binary fission, the first amoeba is still alive), often speaking to the reader (chapter 88 begins with the narrator noting that the book now has as many chapters as a piano has keys).

The novel was originally to be published by Doubleday as they had right-of-first-refusal to Robbins's second book. However Robbins terminated his contract with Doubleday for a better offer from editor Ted Solotaroff and Bantam Books. Bantam was mass-paperback publisher, and they auctioned the rights for hardcover to Houghton Mifflin.

Even Cowgirls Get the Blues was first published in 1976 by Houghton Mifflin. It was concurrently released as both a hardcover and trade paperback novel. It was later released as a mass-market paperback by Bantam Books.